All-trans retinoic acid alleviates collagen-induced arthritis and promotes intestinal homeostasis.

All-trans retinoic acid (ATRA) has emerged as a promising adjunctive treatment for rheumatoid arthritis. However, the mechanism by which ATRA mitigates arthritis remains unclear. In this study, we aimed to explore ATRA alleviation of arthritis and the role of ATRA in regulating intestinal homeostasis. Thus, we established a collagen-induced arthritis (CIA) model in Wistar rats. After 6 weeks of ATRA treatment, the arthritis index of CIA rats decreased, synovial inflammation was alleviated, and the disruption of Th17/Treg differentiation in peripheral blood was reversed. Additionally, the Th17/Treg ratio in the mesenteric lymph nodes decreased and the expression of Foxp3 mRNA increased and that of IL-17 mRNA decreased in the colon and ileum. Microscopically, we observed reduced intestinal inflammation. Transmission electron microscopy revealed that ATRA could repair tight junctions, which was accompanied by an increase in the expression of Claudin-1, Occludin and ZO-1. Moreover, ATRA regulated the composition of the gut microbiota, as was characterized based on the reduced abundance of Desulfobacterota and the increased abundance of Lactobacillus. In conclusion, ATRA demonstrates the potential to alleviate arthritis in CIA rats, which might be correlated with modulating the gut microbiota and regulating the intestinal immune response. Our findings provide novel insights into ATRA-mediated alleviation of arthritis.

Effects of food-grade iron(III) oxide nanoparticles on cecal digesta- and mucosa-associated microbiota and short-chain fatty acids in rats.

Although iron(III) oxide nanoparticles (IONPs) are widely used in diverse applications ranging from food to biomedicine, the effects of IONPs on different locations of gut microbiota and short-chain fatty acids (SCFAs) are unclear. So, a subacute repeated oral toxicity study on Sprague Dawley (SD) rats was performed, administering low (50 mg/kg·bw), medium (100 mg/kg·bw), and high (200 mg/kg·bw) doses of IONPs. In this study, we found that a high dose of IONPs increased animal weight, and 16S rRNA sequencing revealed that IONPs caused intestinal flora disorders in both the cecal digesta- and mucosa-associated microbiota. However, only high-dose IONP exposure changed the abundance and composition of the mucosa-associated microbiota. IONPs increased the relative abundances of Firmicutes, Ruminococcaceae_UCG-014, Ruminiclostridium_9, Romboutsia, and Bilophila and decreased the relative abundance of Bifidobacterium, and many of these microorganisms are associated with weight gain, obesity, inflammation, diabetes, and mucosal damage. Functional analysis showed that changes in the gut microbiota induced by a high dose of IONPs were mainly related to metabolism, infection, immune, and endocrine disease functions. IONPs significantly elevated the levels of valeric, isobutyric, and isovaleric acid, promoting the absorption of iron. This is the first description of intestinal microbiota dysbiosis in SD rats caused by IONPs, and the effects and mechanisms of action of IONPs on intestinal and host health need to be further studied and confirmed.